GLUCOSINOLATES
Glucosinolates yield pungent, sulfur-containing, amino acid-derived aglycones, such as glucobrassicins, thiocyanates, and isothiocyanates, that give Brassicaceae, Capparidaceae, Resedaceae, and other families of plants their unique flavors. Similar to other glycosides, glucosinolates are water soluble, but their aglycones are hydrophobic. These aglycones have an oily consistency and are often known as mustard oils. Despite their strong odor and oily nature, these compounds are chemically very different from volatile oils and should not be confused with them. The sulfur-containing cysteine sulf-oxides that give Allium sativum (garlic) and related plants their pungency and much of their activity are closely related to glucosinolate aglycones. Cysteine sulfoxides do not occur as glycosides.
Isothiocyanate aglycones such as phenethyl isothio-cyanate (PEITC) and sulforaphane and glucobrassicins indole-3-carbinol (I3C) and diindolylmethane (DIM) have been widely studied because of their presence in broccoli and other commonly consumed Brassicaceae vegetables. These compounds have complex effects on cytochrome P450 (CYP) isoforms 1A1, 1A2, and 2B1 in various parts of the body, but ultimately, they tend to decrease hepatic formation of carcinogenic metabolites from a wide variety of environmental chemicals. One of the best studied properties of I3C in particular is its ability to induce the 2-hydrox-ylation catabolic pathway for estradiol, which deprives the 16-alpha and 4-hydroxylation pathways of substrate and appears to greatly reduce the negative effects of estradiol. This is because 2-hydroxylation metabolites are vastly weaker estrogens than 16-alpha- or 4-hydroxylation metabolites.
Glucosinolate aglycones are traditionally used topically as rubefacients. They cause a warming sensation and reddening related to dilation of dermal capillaries. This is traditionally associated with relief from inflammation or pain in deeper or adjacent tissues, possibly caused by gating mechanisms in the spinal cord, although this has not been investigated. Empirically, they also provoke coughing when placed on the chest. If left in place too long, these compounds can cause minor or serious burns.
Glucosinolate aglycones are excreted by the kidneys after conjugation to glutathione by the action of glutathione-5-transferase (GST) or after conjugation to N-acetylcysteine. It has been shown that humans who have the GSTM-1 and GSTT-1 null genotypes do not excrete glucosinolate aglycones efficiently; thus, these stay in their bodies longer after ingestion. This correlates strongly with the anticancer effects of these compounds and helps explain why some people derive protection from cancer by eating Brassicaceae vegetables, while others do not.
Glucosinolates can cause nausea and, in overdose, vomiting. This property is sometimes used in emergencies when no access to medical care is available, to induce vomiting through administration of large quantities of mustard powder. Other adverse effects resulting from internal use have not been documented. Because of their complex effects on CYP enzymes, their use with prescription drugs may cause relevant interactions. For example, it has been shown that reasonable doses of garlic reduce serum levels of protease inhibitors in healthy volunteers, consistent with CYP3A4 induction.
